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Asymptomatic prognosis Alzheimer’s disease blood test

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image: Julia Stockmann and Klaus Gerwert from Bochum Center for Protein Diagnostics
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Using blood tests, German and Dutch research teams predicted the risk of Alzheimer’s disease in people who were clinically diagnosed as not having Alzheimer’s disease but who perceived it as having cognitive impairment (Subjective Cognitive Declined,). SCD). The researchers analyzed blood samples from the SCD cohort supervised at the Alzheimer’s Center in Amsterdam. Using a test called an immuno-infrared sensor developed at Ruhr-Universität Bochum (RUB), the study entry identified all 22 subjects with Alzheimer’s disease, or clinical symptoms, within 6 years. The test also showed subjects with a very low risk of developing Alzheimer’s disease within 6 years.The team will explain the results to the journal Research and treatment of Alzheimer’s disease, Published online on December 24, 2020.

In this study, a team led by Professors of Biophysics Klaus Gerwert and Julia Stockmann of the Bochum Research Center for Protein Diagnostics (Prodi) will study RUB Statistics Professor Nina Timmesfeld, Department of Medical Informatics, Biometrics and Epidemiology, and the University of Amsterdam Medical Center. The Center, Location Vrije University (VUmc), is headed by Professor Charlotte Teunissen and Professor Philip Scheltens.

The sensor detects accidentally folded proteins in the blood

The SCD cohort contained 203 people. At the start of the study, blood samples were taken from all participants and analyzed using a patented immuno-infrared sensor that detects false folding of the amyloid beta (Aβ) peptide, a biomarker for Alzheimer’s disease. It was. In addition, subjects underwent extensive diagnostic testing for Alzheimer’s disease. At the beginning of the study, this did not provide a diagnosis of Alzheimer’s disease in any of the subjects studied. Meanwhile, the immuno-infrared sensor detected the misfolded Aβ peptide at the beginning of the study in all 22 subjects who developed clinical disease over the next 6 years. Subjects who showed mild misfolding took an average longer time (3.4 years) to convert to clinical Alzheimer’s disease than subjects who showed severe Aβ misfolding (2.2 years). I did.

Together with statistician Nina Timsfeld, researchers have predicted the risk of developing clinical Alzheimer’s disease. According to statistical models, SCD subjects with mild misfolding are at 11-fold higher risk, and SCD subjects with severe misfolding are more likely to have no misfolded Aβ peptide in the next 6 years. The risk of developing clinical Alzheimer’s disease is 19 times higher. “Therefore, misfolding of Aβ is a very accurate prognostic plasma biomarker,” Klaus Gerwert concludes.

The combination of the two biomarkers further improves prognosis

In addition, the team confirmed whether the combination of two different measurement methods on the plasma biomarker panel could further improve disease risk prediction. To this end, they combined the misfolding of all Aβ isoforms with a reduced concentration of Aβ42 as a ratio to Aβ40 in plasma. The Amsterdam Group used a new single molecule array (SIMOA) technology to measure Aβ concentration. This improved the accuracy of the assay from AUC (Area Under ROC Curve) 0.94 to 0.99.

“A simple blood test on asymptomatic individuals with subjective concerns has made it possible to predict the risk of developing clinical Alzheimer’s disease in the future with great accuracy,” explains Klaus Gerwert. “But we can equally confidently reveal everything for patients with SCD who are very unlikely to develop Alzheimer’s disease in the next six years.”

“Through the plasma biomarker panel, we can monitor disease progression over a 14-year period, starting with an asymptomatic condition with plaque deposition of Aβ42 in the brain associated with misfolding of Aβ followed by initial cognitive impairment.” Julia Stockmann adds.

Expectations for early treatment

Such blood tests, which can detect the development of Alzheimer’s disease even in the asymptomatic state, are especially useful when active substances are available to treat the disease. In March 2021, the US Food and Drug Administration decides whether to approve the drug aducanumab. “Our results show that drugs for Alzheimer’s disease should be applied as soon as possible in the nonclinical stage to improve the therapeutic response,” said Klaus Gerwert. Bochum researchers are pushing for immuno-infrared sensors that will be used in future study participant selection to achieve significantly better therapeutic responses.

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